Metabolic Complications in Autoimmune and Autoinflammatory Diseases: Pathophysiology, Clinical Implications, and Therapeutic Perspectives

Background and objectives: Autoimmune and autoinflammatory diseases extend far beyond their primary organ manifestations. Systemic inflammation in these disorders disrupts metabolic homeostasis, driving insulin resistance, dyslipidemia, accelerated atherosclerosis, and altered body composition. Metabolic syndrome (MetS) affects approximately 30% of patients with rheumatoid arthritis, with similar or higher prevalence in systemic lupus erythematosus, psoriasis, and antiphospholipid syndrome, contributing substantially to cardiovascular morbidity and mortality yet remaining underrecognized and undermanaged in routine clinical practice. This review summarizes the mechanisms linking chronic inflammation to metabolic dysfunction and the clinical epidemiology of metabolic complications across different autoimmune and autoinflammatory diseases, with attention to the metabolic effects of common immunomodulatory treatments. Methods: This narrative review was based on a literature search of PubMed/MEDLINE, Scopus, and Web of Science (publications available up to March 2026), using search terms covering autoimmune and autoinflammatory diseases, metabolic syndrome, insulin resistance, dyslipidemia, cardiovascular risk, cytokines, adipokines, and immunomodulatory treatments. Results: proinflammatory cytokines, adipokines, and immune cell populations were found to mediate insulin resistance and dyslipidemia across diseases. Conventional disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, and emerging targeted biologics can either ameliorate or worsen metabolic disturbances depending on the specific agent and disease context. Conclusions: Understanding the bidirectional inflammation–metabolism relationship, together with treatment-related metabolic effects, is essential for comprehensive disease management and may identify novel therapeutic targets to reduce cardiovascular burden in this population.